Hand hygiene is the single most important measure to prevent transmission of infectious organisms (VHA Directive 2010-006, MRSA Prevention Initiative). Despite its fundamental place in infection prevention, compliance rates with hand-hygiene protocols remain substantially below target levels. This project will advance the science of hand-hygiene compliance interventions by developing an evidence-based bundle of effective strategies. While many have advocated for a multifaceted bundle as the most effective approach to improving hand-hygiene compliance, no studies have systematically identified an optimal combination of interventions. As such, infection prevention programs continue to use a variety of hand-hygiene interventions without clear evidence of which components in isolation or combination are most effective. The two specific aims and associated hypotheses of CREATE Project 2 include: 1) Identify combinations of hand-hygiene intervention strategies that optimize hand-hygiene compliance and that could form an evidence-based hand-hygiene bundle for VHA implementation. Hypothesis 1: Combinations of interventions will increase compliance rates more than single interventions. Aim 1 will entail a 30-month cluster-randomized controlled trial that will sequentially test three individual hand-hygiene interventions - hand-hygiene point-of-use reminder signs to serve as an environmental cue to action, individual hand sanitizers, and health care worker hand cultures - to identify an optimal combination of interventions to increase hand-hygiene compliance. The trial will be conducted in 59 hospital units in 10 VA hospitals in order to test the efficacy of individual and then sequentially added interventions to determine their incremental impact on hand-hygiene compliance. 2) Identify institutional, organizational, ward/ICU, and individual level facilitators and barriers to implementing hand-hygiene interventions. Hypothesis 2: Facilitators and barriers will pattern around contextual factors suc as level of leadership support and organization of infection control programs. Aim 2 will entail a qualitative process evaluation that includes site visits to purposefully selected sites, semi-structured interviews, and observations to examine barriers and facilitators to the interventions and develop contextual insight for implementing and scaling-up the intervention at additional sites as a national initiative.